The prognostic utility of the "Tumor Burden Score" based on preoperative radiographic features of colorectal liver metastases.

BACKGROUND: Recently, a tumor-burden "metro ticket" score (TBS) based on final pathology was proposed to predict outcome following resection of colorectal liver metastasis (CRLM). We sought to validate the TBS prognostic tool using preoperative radiologic cross-sectional imaging. METHODS: Imaging TBS was defined on a Cartesian plane that incorporated both maximum tumor size (x-axis) and lesion number (y-axis) assessed by pre-operative imaging. The discriminatory power (area under the curve [AUC]) and goodness-of-fit (Harrel's C statistic and Somer's D statistics) of the imaging TBS model was assessed. RESULTS: Imaging and pathologic TBS correlated strongly (r = 0.76, P < 0.01). Among patients treated with neoadjuvant therapy, the correlation was strongest among patients with progressive disease/stable disease (PD/SD) (r = 0.81). Discriminatory power of the imaging-based versus pathology-based TBS models were comparable (AUC 0.64 vs. 0.67, respectively P > 0.05). An incremental worsening of long-term survival was noted as the imaging TBS increased (5-year OS: Zone1, Zone2, and Zone3-61.3%, 46.7%, and 38.5%, respectively; P = 0.03). The imaging-based TBS model outperformed the "classic" pathology-based Fong score (Harrel's C-index: imaging TBS-0.56 vs. Fong score-0.53; Somers'D-index: imaging TBS-012 vs. Fong score-0.06). CONCLUSIONS: Imaging-based TBS was superior to traditional tumor size and number and was comparable to pathology-based TBS. Imaging-based TBS may have the potential to facilitate improved preoperative risk stratification of patients with CRLM.

Systemic treatment and primary tumor location in patients with metastatic colorectal cancer.

PURPOSE: Tumor location (right-sided vs. left-sided) is known to exert a significant influence on the prognosis of primary colorectal cancer (CRC). Given the genetic continuity between primary and metastatic lesions, we aimed to summarize the existing literature on the prognostic implications of primary tumor site as well as to examine the response to chemotherapy by primary tumor location in patients with metastatic CRC (mCRC). METHODS: A structured review of the literature was performed between 6/1/2016-7/1/2016 using the Pubmed database. Original research articles published between 1/1/2000- 07/01/2016 were considered eligible. The primary endpoints were overall survival (OS)/ progression free survival (PFS) and response to systemic treatment in patients with mCRC. RESULTS: Eleven studies were included. Tumor site was a strong independent predictor of worse OS/PFS in 9 studies, with right-sided tumors having worse prognosis in all cases. Furthermore, 6 studies demonstrated an inferior response to systemic treatment or worse prognosis following the administration of specific regimens among patients with right-sided cancers. As such, there is significant evidence that right-sided lesions are associated with poor outcomes and resistance to systemic treatment. CONCLUSION: Consequently, primary tumor location should be a consideration, when the administration of systemic therapy is contemplated in mCRC.

Diagnostic intervals and pancreatic ductal adenocarcinoma (PDAC) resectability: a single-center retrospective analysis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) often presents with nonspecific symptoms and the workup is not standardized. To study the impact of delays in diagnosis and in the initiation of treatment, we investigated the relationship between length of diagnostic intervals and surgical resectability. METHODS: We performed a retrospective chart review of patients evaluated for PDAC at Johns Hopkins in 2014. Data were collected on the patient (date of first symptoms-first medical appointment), diagnostic (first medical appointment-diagnosis of PDAC), and treatment (diagnosis of PDAC-1st day of treatment) time intervals, and the upfront treatment received. Asymptomatic patients diagnosed incidentally, or for whom records were incomplete, were excluded from analysis. RESULTS: Of 453 charts reviewed, 116 patients met inclusion criteria. The median patient interval was 14 days [interquartile range (IQR): 6-30 days], the median diagnostic interval was 22 days (IQR: 8-46 days), and the median treatment interval was 26 days (IQR: 15-35 days). Thirty-eight patients (33%) received upfront surgery and 78 (67%) received nonsurgical treatment. After adjusting for multiple factors, the odds of receiving surgery significantly increased for individuals with a patient interval of 30 days or less [adjusted odds ratio (aOR): 3.41; 95% confidence interval (CI): 1.08-13.20; P=0.050] and with a diagnostic interval of 60 days or less (aOR: 15.68; 95% CI: 2.95-291.00, P=0.009). CONCLUSIONS: A patient interval less than 1 month and a diagnostic interval less than 2 months for symptomatic PDAC are associated with increased odds of upfront surgical resection. These data provide initial evidence that reducing diagnostic delays may lead to improved outcomes in PDAC.

The Prognostic Value of Varying Definitions of Positive Resection Margin in Patients with Colorectal Cancer Liver Metastases.

BACKGROUND: Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width = 0 mm) or a margin width < 1 mm. Consequently, patients with a margin width of 0-1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins. METHODS: Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin. RESULTS: Five hundred thirty-nine (85.2%) patients had a margin width ≥ 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥ 1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P < 0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04-2.67; P = 0.04, and HR 2.14, 1.46-3.16; P < 0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41-2.65; P < 0.001). CONCLUSIONS: Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width > 1 mm. Consequently, a uniform definition of R1 as a margin width < 1 mm should perhaps be employed by future studies.

Double KRAS and BRAF Mutations in Surgically Treated Colorectal Cancer Liver Metastases: An International, Multi-institutional Case Series.

BACKGROUND: While previously believed to be mutually exclusive, concomitant mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS)- and V-raf murine sarcoma b-viral oncogene homolog B1 (BRAF)-mutated colorectal carcinoma (CRC), has been described in rare instances and been associated with advanced-stage disease. The present case series is the first to report on the implications of concurrent KRAS/BRAF mutations among surgically treated patients, and the largest set of patients with surgically treated colorectal liver metastasis (CRLM) and data on KRAS/BRAF mutational status thus far described. CASE SERIES: We present cases from an international, multi-institutional cohort of patients that underwent hepatic resection for CRLM between 2000-2015 at seven tertiary centers. The incidence of KRAS/BRAF mutation in patients with CRLM was 0.5% (4/820). Of these cases, patient 1 (T2N1 primary, G13D/V600E), patient 2 (T3N1 primary, G12V/V600E) and patient 3 (T4N2 primary, G13D/D594N) succumbed to their disease within 485, 236 and 79 days respectively, post-hepatic resection. Patient 4 (T4 primary, G12S/G469S) was alive 416 days after hepatic resection. CONCLUSION: The present case series suggests that the incidence of concomitant KRAS/BRAF mutations in surgical cohorts may be higher than previously hypothesized, and associated with more variable survival outcomes than expected.